On September 4, 2018 IntegraGen (FR0010908723: ALINT – PEA-SME Eligible), a company specializing in the transformation of data from biological samples into genomic information and diagnostic tools for oncology, reported the publication of the results of a definitive study reporting on the analysis of the expression of miR-31-3p in tumors from 370 RAS wild-type (WT) metastatic colorectal cancer (mCRC) patients enrolled in the FIRE-3 clinical trial (AIO KRK-0306) (Press release, Integragen, SEP 4, 2018, View Source [SID1234529334]). The paper, entitled "Validation of miR-31-3p Expression Level to Predict Cetuximab Efficacy When Used as First-Line Treatment in RAS Wild-Type Metastatic Colorectal Cancer" was published online in Clinical Cancer Research, a leading oncology journal which focuses on innovative clinical and translational cancer research studies that bridge the laboratory and the clinic.

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The study found that a low expression of the miR-31-3p biomarker predicts both improved survival and treatment response in patients receiving anti-EGFR therapy. In addition to confirming miR-31-3p is predictive of outcomes for RAS WT mCRC patients treated with anti-EGFR therapy, the study also found that patients with a miR-31-3p expression below a pre-defined threshold have a one year longer median overall survival, a 40% reduction in mortality risk, and a better treatment response when they are treated with FOLFIRI plus cetuximab compared to FOLFIRI plus bevacizumab. Conversely, no difference in outcomes was seen between the two treatment groups in patients with miR-31-3p expression above the pre-defined threshold. These results support the use of miR-31-3p expression testing in primary tumors from RAS WT mCRC patients to assist clinicians to identify the most appropriate first line biologic therapy may be most beneficial.

"The results of our study demonstrate the ability for miR-31-3p to predict which patients with RAS wild-type metastatic colorectal cancer will have improved outcomes when treated in first line with cetuximab compared to bevacizumab when combined with FOLFIRI therapy," explained Prof. Dr. Sebastian Stintzing, an oncologist from University Hospital, LMU Munich in Munich, Germany and lead author on the paper. "These findings are particularly significant since nearly two-thirds of the patients with RAS wild-type tumors in our study had low miR-31-3p expression levels and would therefore benefit from being treated with cetuximab versus bevacizumab as first line therapy for mCRC."

"The results from this study confirm the ability of the miR-31-3p biomarker to predict anti-EGFR therapy response, and in turn, demonstrates the clinical utility of this biomarker for patients with metastatic colorectal cancer," stated Dr. Bernard Courtieu, IntegraGen’s CEO. "This data demonstrates that the use of miR-31-3p expression testing can guide the choice of first line biologic therapy in RAS wild-type patients and enable oncologists to better select a personalized therapeutic approach, resulting in an improved opportunity for positive patient outcomes and decreased cost of care."

IntegraGen will presenting new data reporting positive results from an analysis of miR-31-3p expression in over 1,400 resected stage III colon cancer patients enrolled in the PETACC-8 trial during the upcoming 2018 Annual Meeting of the European Society for Medical Oncology October 19-23 in Munich, Germany.

IntegraGen has commercialized the miRpredX 31-3p kit, a proprietary IVD CE Marked kit and has also licensed its intellectual property associated with miR-31-3p to GoPath Laboratories for the North American market. GoPath Labs recently announced the commercial launch of miR-31now, a laboratory developed test which measures miR-31-3p expression in FFPE specimens.

ABOUT THE FIRE-3 CLINICAL TRIAL

The FIRE-3 (AIO KRK-0306) clinical trial is an independent, randomized, controlled Phase III trial conducted in Europe and led by University Hospital, LMU Munich, Germany. The study compares outcomes of KRAS Exon 2 wild-type (WT) stage IV colorectal cancer patients randomized to receive FOLFIRI therapy (5-FU, folinic acid and irinotecan) in combination with either cetuximab or bevacizumab.

On September 4, 2018 Asterias Biotherapeutics, Inc. (NYSE American: AST), a biotechnology company dedicated to developing cellular immunotherapies to treat cancer and cell-based therapeutics to treat neurological conditions associated with demyelination, reported that the Safety Review Committee (SRC) for the first clinical trial of VAC2 has held its second scheduled meeting to review the safety and tolerability data generated in patients two and three enrolled in the study and recommended continuation of the study and moving to open enrollment in the advanced disease cohort (Arm A), as planned per the study’s protocol (Press release, Asterias Biotherapeutics, SEPT 4, 2018, View Source;date=September+04%2C+2018&title=Asterias+Biotherapeutics+Announces+Positive+Outcome+from+Second+Safety+Review+Committee+Meeting+and+Open+Enrollment+for+VAC2+Clinical+Trial+in+Non-Small+Cell+Lung+Cancer+%28NSCLC%29 [SID1234529352]). This initial clinical trial, which is being sponsored, managed and funded by Cancer Research UK, will examine the safety and tolerability of VAC2 in NSCLC as the study’s primary endpoints. Secondary and tertiary endpoints of the study include evaluations of the immunogenicity of VAC2 in NSCLC.

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"We are encouraged that VAC2 was found to be safe and well-tolerated in all three patients and are enthusiastic for Cancer Research UK to begin open enrollment of the advanced disease cohort," commented Dr. Edward Wirth, Chief Medical Officer of Asterias Biotherapeutics. "Cancer Research UK recently opened a second site in Birmingham, England to support enrollment and we are pleased with how the study is progressing."

The Safety Review Committee has now reviewed accumulated safety data generated to date for the first three patients in the advanced disease cohort. Each patient has now received all six weekly doses of 10 million VAC2 cells per protocol.

As specified in the VAC2 clinical trial protocol, the Safety Review Committee meets on a dosing-driven basis to review safety and tolerability data from the ongoing trial. The Committee is comprised of a group of medical and scientific experts and is responsible for reviewing and evaluating patient safety data in order to safeguard the wellbeing of trial participants.

About VAC2

VAC2 is an innovative immunotherapy product that contains mature dendritic cells derived from pluripotent stem cells. These non-patient specific (allogeneic) VAC2 cells are engineered to express a modified form of telomerase, a protein widely expressed in tumor cells, but rarely found in normal cells. The modified form of telomerase invokes enhanced stimulation of immune responses to the protein. Similar to an earlier, Asterias-sponsored, hematological cancer program using an autologous approach, the VAC2 dendritic cells instruct the immune system to generate responses against telomerase and, through this mechanism, target tumor cells. VAC2’s mode of action is complementary to and potentially synergistic with other immune therapies such as checkpoint inhibitors or other immune pathway inhibitors.

About Non-Small Cell Lung Cancer and the VAC2 Trial

Lung cancer (both small cell and non-small cell) is the leading cause of cancer-related death, accounting for about one-quarter of all cancer deaths and more than colorectal, breast, and prostate cancers combined. Non-small cell lung cancer (NSCLC) accounts for about 80% to 85% of lung cancers, according to the American Cancer Society. The three main types of NSCLC are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. The American Cancer Society’s estimates for lung cancer in the United States for 2017 are: about 222,500 new cases of lung cancer, and about 155,870 deaths from lung cancer. Despite the large number of people afflicted by non-small cell lung cancer, patients remain vastly underserved due to a scarcity of effective treatments. According to statistics published by Cancer Research UK, the five year survival rate for lung cancer patients in England and Wales is less than 10%.

As currently designed, the first VAC2 clinical trial will enroll up to 24 subjects into one of two cohorts, depending on the stage of their non-small cell lung cancer. The first cohort will evaluate VAC2 in up to 12 subjects with advanced non-small cell lung cancer. Subjects in this cohort, who carry the major histocompatibility gene, HLA-A2, will receive six weekly injections of VAC2 and will be followed for safety, immune responses to telomerase and overall clinical survival. These survival results will be compared directly to a control group who meet all of the other inclusion/exclusion criteria but do not possess the HLA-A2 gene. Assuming safety is demonstrated in the first cohort, enrolment will advance to a second cohort. In the second cohort, early stage subjects who have had successful resection of their tumour with no evidence of metastasis will be enrolled. Up to 12 subjects in this second cohort who carry the major histocompatibility allele HLA-A2 will receive six, weekly injections of VAC2 and will be followed for safety, immune responses to telomerase, overall clinical survival and time to relapse. These survival results will again be compared directly to a control group who meet all of the inclusion/exclusion criteria of cohort 2 but are not HLA-A2+. Subjects will be followed for one year for immune response to telomerase and for 2 years for the survival endpoints. The supply of VAC2 to be used in this trial is being manufactured by Cancer Research UK’s Biotherapeutics Development Unit. Asterias and Cancer Research UK are exploring the combination of VAC2 with an immune pathway inhibitor.

On September 4, 2018 Pieris Pharmaceuticals, Inc. (NASDAQ: PIRS), a biotechnology company advancing novel biotherapeutics through its proprietary Anticalin technology platform for cancer, respiratory and other diseases, reported that it has dosed the first patient in the Company’s Phase 1 combination clinical trial of PRS-343, its lead proprietary immuno-oncology drug candidate targeting HER2 and 4-1BB, plus atezolizumab (Tecentriq), an approved PD-L1 inhibitor (Press release, Pieris Pharmaceuticals, SEP 4, 2018, View Source [SID1234529394]).

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The trial, a multicenter, open-label, Phase 1 dose escalation study, is designed to determine the safety, tolerability, and potential synergistic anti-tumor effects of PRS-343 plus anti-PD-L1 immunotherapy in patients with advanced or metastatic HER2-positive solid tumors. Elevated HER2 expression is associated with multiple cancers, including gastroesophageal, bladder, breast, and a range of other tumor types. The trial is fully funded and sponsored by Pieris, while Roche is supplying atezolizumab.

"The initiation of the combination trial of PRS-343 with an anti-PD-L1 immunotherapy marks the beginning of Pieris’ investigation into the potential synergistic effects of its 4-1BB-targeted therapy with PD-1/L1 blockade," said Louis Matis, M.D., Senior Vice President and Chief Development Officer of Pieris. "Given evidence from multiple preclinical studies demonstrating synergistic anti-tumor activity from concurrent 4-1BB activation and PD-(L)1 pathway blockade, we believe that combination therapy with PRS-343 and atezolizumab has the potential to provide significant clinical benefit for patients. We are enthusiastic to be initiating this trial and look forward to reporting our findings from this combination study next year."

About PRS-343

PRS-343 is a bispecific monoclonal antibody-Anticalin fusion protein comprised of a HER2 tumor-targeting antibody genetically linked to a potent Anticalin specific for the immune costimulatory TNF family receptor 4-1BB (CD137). PRS-343 is being developed as the first 4-1BB based bispecific therapeutic to mediate the activation of tumor-specific T lymphocytes selectively within the tumor microenvironment (TME). 4-1BB is a potent costimulatory immunoreceptor and an established marker for tumor-specific infiltrating T lymphocytes, and is, therefore, an attractive target for cancer immunotherapy. In in vivo preclinical tumor models, PRS-343 has demonstrated potent T lymphocyte activation localized to the TME of established HER2-positive tumors, indicating the potential for both enhanced safety and efficacy.

About HER2-Positive Malignancies

HER2 is a tyrosine kinase receptor growth-promoting protein found on the surface of some cancer cells and is associated with aggressive disease progression. Multiple tumor types can express HER2 including breast, gastroesophageal, bladder, biliary (cholangiocarcinoma), colorectal, endometrial, ovarian, non-small cell lung, pancreatic, head and neck, and other cancers.

On September 4, 2018 Puma Biotechnology, Inc. (Nasdaq:PBYI) reported that the European Commission (EC), has granted marketing authorisation for NERLYNX (neratinib) for the extended adjuvant treatment of adult patients with early stage hormone receptor positive HER2-overexpressed/amplified breast cancer and who are less than one year from the completion of prior adjuvant trastuzumab based therapy (Press release, Puma Biotechnology, SEPT 4, 2018, View Source [SID1234529268]).

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EC approval was based on the Phase III ExteNET trial, a multicenter, randomized, double-blind, placebo-controlled trial of neratinib following adjuvant trastuzumab treatment. Patients (n=2,840) with early stage HER2-positive breast cancer and within two years of completing adjuvant trastuzumab were randomized to receive either neratinib (n=1420) or placebo (n=1420) for one year.

The results of the ExteNET trial demonstrated that after two years of follow-up, for patients with hormone receptor positive, HER2-positive early stage breast cancer patients who were treated within one year after the completion of trastuzumab based adjuvant therapy, invasive disease-free survival (iDFS) was 95.3% in the patients treated with neratinib compared with 90.8% in those receiving placebo (hazard ratio = 0.49; 95% CI: (0.30, 0.78); p=0.002)

The most common adverse reactions (>5%) were diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, AST or ALT increase, nail disorder, dry skin, abdominal distention, weight loss, and urinary tract infection. The most common adverse reaction leading to discontinuation was diarrhea, which was observed in 16.8% of neratinib-treated patients. Hepatotoxicity or increases in liver transaminases led to drug discontinuation in 1.7% of neratinib-treated patients.

"Reducing the risk of disease recurrence remains a need for patients, despite advances in the treatment of early stage HER2-positive breast cancer," said Puma Biotechnology CEO and President Alan H. Auerbach. "We are pleased to bring this new medicine to patients in Europe and would like to express our appreciation to the patients, caregivers and physicians who contributed to the neratinib clinical development program and, more specifically, the ExteNET trial. We are committed to continuing to expand NERLYNX accessibility to patients worldwide. We expect NERLYNX to be commercially available in Europe in 2019, beginning with our launch in Germany during the first half of 2019 and followed by additional countries throughout Europe in the second half of 2019."

The approval of NERLYNX by the European Commission follows the positive opinion issued by the Committee for Medicinal Products for Human Use of the European Medicines Agency in June 2018.

Neratinib was approved by the U.S. Food and Drug Administration (FDA) in July 2017 for the extended adjuvant treatment of adult patients with early stage HER2-positive breast cancer following adjuvant trastuzumab-based therapy, and is marketed in the United States as NERLYNX (neratinib) tablets.

About HER2-Positive Breast Cancer

Approximately 20 to 25 percent of breast cancer tumors over-express the HER2 protein. HER2-positive breast cancer is often more aggressive than other types of breast cancer, increasing the risk of disease progression and death. Although research has shown that trastuzumab can reduce the risk of early stage HER2-positive breast cancer returning after surgery, up to 25% of patients treated with trastuzumab experience recurrence.

On September 4, 2018 Thermo Fisher Scientific Inc. (NYSE: TMO), the world leader in serving science, reported that Marc N. Casper, president and chief executive officer, will present at the Morgan Stanley Global Healthcare Conference on Wednesday, September 12, 2018, at 2:15 p.m. (ET) at the Grand Hyatt New York, New York (Press release, Thermo Fisher Scientific, SEP 4, 2018, View Source [SID1234529458]).

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You can access the live webcast of the presentation via the Investors section of our website, www.thermofisher.com.